Navigating European NB Opinion for Drug-Device Combination Products (A Comprehensive Guide)
A European Notified Body (NB) Opinion is required under Article 117 of EU MDR (EU) 2017/745 for certain integral drug-device combination products where the device component is not already CE marked for its intended purpose. The Notified Body reviews the device documentation and confirms compliance with the applicable General Safety and Performance Requirements (GSPRs), supporting the Marketing Authorization Application (MAA).
Introduction
As drug-device combination products become increasingly common in modern healthcare, manufacturers must navigate both pharmaceutical and medical device regulations before introducing their products to the European market. One of the most significant regulatory requirements introduced by EU MDR (EU) 2017/745 is the European Notified Body (NB) Opinion, established under Article 117.
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For many manufacturers, the NB Opinion process is one of the most challenging stages of regulatory approval. Questions such as “Does my product require an NB Opinion?”,
“What documentation must be submitted?”, and “How does the Notified Body evaluate the device component?” are common during product development.
Understanding these requirements early allows manufacturers to develop a compliant regulatory strategy, prepare complete technical documentation, and minimize delays during the Marketing Authorization process.
This guide explains the European NB Opinion process, identifies when Article 117 applies, outlines the documentation expected by a Notified Body, and shares practical recommendations for achieving a smoother regulatory review.
What Is a European NB Opinion?
A European Notified Body (NB) Opinion is an independent regulatory assessment confirming that the medical device component of certain drug-device combination products complies with the relevant General Safety and Performance Requirements (GSPRs) of EU MDR (EU) 2017/745.
Unlike a traditional CE Certificate, an NB Opinion focuses specifically on the integrated medical device within a medicinal product. It provides assurance to regulatory authorities that the device component has been independently assessed and found to meet the applicable safety and performance requirements.
The NB Opinion forms an important part of the Marketing Authorization Application (MAA) submitted for medicinal products incorporating an integral medical device.
Why Was Article 117 Introduced?
Before the implementation of the EU MDR, many integral drug-device combination products were assessed primarily under medicinal product legislation, with limited independent evaluation of the medical device component.
To strengthen patient safety and improve regulatory oversight, Article 117 introduced an additional conformity assessment requirement for specific products.
The objective of Article 117 is to:
- Improve the safety of integrated medical devices
- Ensure compliance with EU MDR requirements
- Harmonize regulatory expectations across the European Union
- Strengthen confidence in combination products entering the market
- Reduce risks associated with poorly evaluated device components
Rather than replacing medicinal product legislation, Article 117 complements it by requiring an independent review of the medical device component where applicable.
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Which Products Require an NB Opinion?
Not every combination product requires a European NB Opinion. The requirement depends on how the product is classified and whether the medical device component has already undergone conformity assessment.
An NB Opinion is generally required when:
- The medicinal product incorporates a medical device as an integral component.
- The device component is not already CE marked for its intended purpose.
- The applicable conformity assessment under the EU MDR requires Notified Body involvement.
Examples may include:
- Prefilled syringes
- Auto-injectors
- Insulin pens
- Certain infusion systems
- Metered-dose inhalers
- Drug delivery devices integrated with medicinal products
Determining whether Article 117 applies should be one of the earliest regulatory activities during product development, as it directly influences documentation requirements and submission planning.
European NB Opinion Process: Step-by-Step
Obtaining a European NB Opinion requires careful planning and complete technical documentation. While the exact review process may vary between Notified Bodies, manufacturers typically follow the sequence below.
Step | Activity | Responsible Party |
1 | Determine product classification | Manufacturer |
2 | Confirm Article 117 applicability | Manufacturer |
3 | Prepare technical documentation | Manufacturer |
4 | Select an appropriate Notified Body | Manufacturer |
5 | Submit the documentation package | Manufacturer |
6 | Technical review and conformity assessment | Notified Body |
7 | Respond to review questions and deficiencies | Manufacturer |
8 | Issue of European NB Opinion | Notified Body |
Each stage builds upon the previous one, making early regulatory planning critical for avoiding unnecessary review cycles.
Many manufacturers believe the NB Opinion process begins when documents are submitted to a Notified Body. In practice, successful submissions begin much earlier—with product classification, regulatory strategy, and the preparation of complete technical documentation. Early planning significantly reduces the likelihood of deficiencies during the review.
Documentation Required for a European NB Opinion
The quality and completeness of the technical documentation play a significant role in the outcome of the NB Opinion process. A well-prepared dossier enables the Notified Body to efficiently assess whether the medical device component complies with the applicable requirements of EU MDR (EU) 2017/745.
Although documentation requirements vary depending on the product and regulatory pathway, manufacturers are generally expected to provide:
- Device description and intended use
- Product architecture showing the integration of the drug and device
- General Safety and Performance Requirements (GSPR) checklist
- Risk Management File aligned with ISO 14971
- Design verification and validation reports
- Clinical evaluation or performance evidence supporting the device component
- Usability engineering documentation (where applicable)
- Manufacturing and quality management information
- Labeling and Instructions for Use (IFU)
- Declaration of conformity (where applicable)
The documentation should clearly demonstrate that the device component is safe, performs as intended, and complies with the relevant EU MDR requirements.
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Best Practices for a Successful NB Opinion Submission
Preparing for a European NB Opinion should begin during product development rather than immediately before regulatory submission. A structured approach helps manufacturers reduce review cycles and improve submission quality.
Determine the Regulatory Pathway Early
Confirm whether Article 117 applies and establish the appropriate regulatory strategy before product development progresses.
Prepare Documentation Continuously
Develop technical documentation alongside product design instead of compiling it at the end of the project.
Perform a Gap Assessment
Review the documentation against EU MDR requirements to identify missing information before submission.
Strengthen Risk Management
Ensure the Risk Management File is complete, current, and supported by objective evidence throughout the product lifecycle.
Engage the Notified Body Early
For complex combination products, early communication with the selected Notified Body can help clarify expectations and reduce the likelihood of avoidable deficiencies
Regulatory Timeline
Although review durations vary depending on the product complexity and the selected Notified Body, the overall process generally follows this sequence:
Phase | Activity |
Planning | Product classification and regulatory strategy |
Documentation | Preparation of the technical documentation package |
Submission | Submission to the selected Notified Body |
Review | Technical assessment and requests for clarification |
Response | Manufacturer addresses deficiencies and provides additional evidence |
Outcome | European NB Opinion issued upon successful assessment |
Note: Review timelines vary considerably based on the completeness of the submission, the complexity of the product, and the workload of the selected Notified Body. Manufacturers should avoid relying on fixed timelines when planning product launches.
Many manufacturers assume that obtaining a European NB Opinion is primarily an administrative process. In reality, it is a technical assessment of the medical device component. The strongest submissions are those supported by complete technical documentation, clear GSPR mapping, robust risk management, and well-documented verification and validation activities.
How Operon Strategist Supports the European NB Opinion Process
Obtaining a European NB Opinion requires careful planning, technical expertise, and a clear understanding of both medical device and medicinal product regulations. Operon Strategist helps manufacturers prepare compliant submissions that align with the expectations of European regulatory authorities and Notified Bodies.
Our support includes:
- Regulatory pathway assessment
- Article 117 applicability review
- Product classification and PMOA evaluation
- Technical documentation preparation and review
- GSPR compliance assessment
- Risk management documentation
- Gap assessment before submission
- Coordination with Notified Bodies
- End-to-end regulatory strategy for global market access
Whether you are preparing your first Article 117 submission or expanding an existing product portfolio into Europe, our regulatory experts help simplify the process and reduce compliance risks.
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FAQ's
What is a European NB Opinion?
A European NB Opinion is an independent assessment issued by a Notified Body confirming that the medical device component of certain integral drug-device combination products complies with the applicable requirements of EU MDR (EU) 2017/745.
When is an NB Opinion required?
An NB Opinion is generally required under Article 117 when an integral drug-device combination product contains a medical device component that is not already CE marked for its intended purpose.
Is an NB Opinion the same as CE Marking?
No. A CE Certificate confirms conformity for a medical device placed on the market under the EU MDR. An NB Opinion supports the Marketing Authorization Application for certain medicinal products incorporating an integral medical device.
What documents are reviewed by the Notified Body?
The Notified Body typically reviews technical documentation, GSPR compliance, risk management documentation, verification and validation evidence, clinical or performance data, labeling, and manufacturing information related to the device component.
Can manufacturers choose any Notified Body?
Manufacturers should select a Notified Body that is designated for the relevant scope of the medical device component and has appropriate expertise in the applicable technologies.